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Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: http://www.tandfonline.com/loi/gpss20
Selective access to sulfurated and selenated heterocycles by intramolecular cyclization of βsubstituted sulfides and selenides Antonella Capperucci, Cynthia Salles, Simone Scarpelli & Damiano Tanini To cite this article: Antonella Capperucci, Cynthia Salles, Simone Scarpelli & Damiano Tanini (2017) Selective access to sulfurated and selenated heterocycles by intramolecular cyclization of β-substituted sulfides and selenides, Phosphorus, Sulfur, and Silicon and the Related Elements, 192:2, 172-174, DOI: 10.1080/10426507.2016.1252364 To link to this article: http://dx.doi.org/10.1080/10426507.2016.1252364
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Date: 12 January 2017, At: 10:06
PHOSPHORUS, SULFUR, AND SILICON , VOL. , NO. , – http://dx.doi.org/./..
Selective access to sulfurated and selenated heterocycles by intramolecular cyclization of β-substituted sulfides and selenides Antonella Capperucci, Cynthia Salles, Simone Scarpelli, and Damiano Tanini Dipartimento di Chimica “Ugo Schiff”, Università di Firenze, Sesto Fiorentino, Firenze, Italy
ABSTRACT
δ-Hydroxy- and δ-amino α-thio-esters, easily obtainable through S-alkylation of β-mercapto alcohols and β-amino thiols with bromo acetate, behave as suitable starting compounds to obtain various 2-hydroxy-1,4oxathianes and (S)-3,4-dihydro-2H-1,4-thiazines via a reductive ring closure. Under similar conditions, selenated heterocycles are also synthesized.
GRAPHICAL ABSTRACT
Introduction A variety of sulfur containing heterocyclic compounds are contained in natural products, drug molecules, and food flavors. Also, selenated heterocycles represent a very interesting class of molecules due to their useful reactivity in organic synthesis and their potential biological applications1 . Among the various heterocyclic compounds, six-membered 1,4-heterocycles have attracted considerable attention for their properties in medicinal and biological field, and for their use in organic synthesis2 . 1,4-Oxathiane derivatives possess for instance antitumor3 , antibacterial4 and antifungal activity2a , and find application as chiral auxiliaries for asymmetric transformations5 . Replacement of oxygen with sulfur in thiomorpholines allows to obtain compounds with antioxidant and hypolipidemic activity6 , and to access derivatives that can behave as DPP-IV inhibitors7 . Several methods are reported for obtaining 1,4-oxathianes5,8 and thiomorpholines6,8 . On the contrary, to the best of our knowledge, few examples are described for obtaining the seleno-analogues 1,4-oxaselenanes9 and selenomorpholines10 , the latter showing an interesting antibiotic activity10b,11 . Our interest in the chemistry of thiosilanes led us to disclose a selective and general methodology to access β-substituted thiols, which were demonstrated as useful reagents for the synthesis of 2-silyl five-membered heterocycles12 and 1,2,5-trithiepanes13 . More recently, we discovered that also selenosilanes were able to react with strained molecules, leading to a selective formation of
ARTICLE HISTORY
Received October Accepted October KEYWORDS
-Hydroxy-,-oxathianes; ,-dihydro-H-,-thiazines; -hydroxy-,-selenanes; ,dihydro-H-,-selenazines; ring closure
β-functionalized selenides, diselenides14 and various five- and seven-membered thia(seleno) heterocycles13,15 . On the basis of these results, we then moved to explore the behavior of β-substituted sulfides and selenides to synthesize sulfurated and selenated six-membered 1,4-heterocycles.
Results and discussion We reasoned that a convenient access to chalcogen containing hexaatomic heterocycles could be the functionalization of suitable substituted δ-hydroxy or δ-amino α-thio-esters (Figure 1). The latter could be obtained through reaction of β-substituted thiols with a α-bromo ester. Thus, β-mercapto alcohols 2, easily obtained through reaction of bis(trimethylsilyl)sulfide (HMDST) 1 and variously substituted epoxides16 , were treated with bromo acetate (Scheme 1, X = O), in the presence of Cs2 CO3 /TBAI system17 . Under these conditions, a clean S-alkylation occurred, leading to the corresponding δ-hydroxy-α-thioesters 3 in good yields. Reduction with DIBAL-H allowed the formation of differently 6substituted 2-hydroxy-1,4-oxathianes 4 as equimolar mixture of diastereoisomers, via a spontaneous intramolecular cyclization of the intermediate aldehyde (Scheme 1, X = O)18 . In order to evaluate the scope of this procedure, a chiral β-amino thiol 5, obtained from aziridine and HMDST12 , was reacted with the bromo ester under similar conditions, affording the Ts-protected α-thio-δ-amino esters 6 (Scheme 1,
CONTACT Antonella Capperucci antonella.capperucci@unifi.it Dipartimento di Chimica “Ugo Schiff”, Università di Firenze, Via della Lastruccia -, Sesto Fiorentino (Firenze), Italy. Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/gpss. © Taylor & Francis Group, LLC
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Figure . Retrosyntetic approach to six-membered ,-heterocycles.
Scheme . Synthesis of thiaheterocycles.
Scheme . Synthesis of Se-containing heterocycles.
X = NTs). Treatment under reducing conditions led this time to the isolation of the corresponding aldehyde 7. The aldehyde undergoes cyclization in d-chloroform, while recording NMR spectra, leading to (S)-3-isopropyl-4-tosyl-3,4-dihydro-2H-1,4thiazine 8, after water elimination. Expanding the scope of this procedure to seleno analogues, we found that the precursor β-hydroxy selenide 10 could be achieved by treatment of selenol (obtained from the epoxide and (TMS)2 Se 9)19 with the bromo ester (Scheme 2) under Cs2 CO3 /TBAI activation. Treatment with DIBAL-H directly afforded differently 6-substituted 2-hydroxy 1,4-oxaselenolanes 11 as mixture of stereoisomers20 .
Conclusions This approach represents a convenient method for the preparation of six-membered chalcogen-containing heterocycles. Further work to extend this methodology to differently functionalized sulfur and seleno heterocycles is now in progress in our laboratory.
References 1. Inter alia: a) Mugesh, G.; du Mont, W.-W.; Sies, H. Chem. Rev. 2001, 101, 2125-2179. b) Tiecco, M.; Testaferri, L.; Bagnoli, L.; Marini, F.; Santi, C.; Temperini, A.; Sternativo, S.; Terlizzi, R.; Tomassini, C. Arkivoc. 2006, vii, 186-206. c) J. Młochowski, J.; Kloc, K.; Lisiak, R.; Potaczek, P.; Wójtowicz, H. Arkivoc. 2007, vi, 14-46. 2. a) Cook, M. J. Comprehensive Heterocyclic Chemistry; Katrizky, A. R.; Rees, C. W., Eds.; Pergamon Press: Oxford, 1984, Vol. 3, 943-994. b) Matlock, J. V.; Svejstrup, T. D.; Songara, P.; Overington, S.; McGarrigle, E. M.; Aggarwal, V. K. Org. Lett. 2015, 17, 5044-5047 and references cited therein. 3. Miyauchi, H.; Tanio, T.; Ohashi, N. Bioorg. Med. Chem. Lett. 1996, 6, 2377-2380. 4. Kim, J. W.; Park, H. B.; Chung, B. Y. Bull. Korean Chem. Soc. 2006, 27, 1164-1170. 5. Gharpure, S. J.; Anuradha, D.; Prasad, J. V. K.; Rao, P. S. Eur. J. Org. Chem. 2015, 86–90, and references cited therein.
6. Tooulia, K.-K.; Theodosis-Nobelos, P.; Rekka Arch. Pharm. Chem. Life Sci. 2015, 348, 629–634, and references cited therein. 7. a) Han, B.; Liu, J. L.; Huan, Y.; Li, P.; Wu, Q.; Lin, Z. Y.; Shen, Z. F.; Yin, D. L.; Huang, H. H. Chin. Chem. Lett. 2012, 23, 297-300. b) Li, S.; Zhong, W.; Xiao, J.; Ma, X.; Wang, L.; Liu, H.; Zheng, P. PCT Int. Appl. (2008), WO 2008119208 A1 20081009. 8. Samzadeh-Kermani, A. Synlett. 2014, 1839–1842, and references cited therein. 9. Potapov, V. A.; Musalov, M. V.; Abramova, E. V.; Musalova, M. V.; Rusakov, Y. Y.; Amosova, S. V. Chem. Heterocycl. Compd. 2014, 49, 1821-1826. 10. a) Martynov, A. V.; Makhaeva, N. A.; Amosova, S. V. J. Sulfur. Chem. 2014, 35, 502-511. b) Xi, L.; Yi, L.; Jun, W.; Songsheng, Q. Thermochim. Acta. 2001, 375, 109-113. 11. Xi, L.; Yi, L.; Ruming, Z.; Jun, W.; Xuesong, S.; Songsheng, Q. Biol. Trace Elem. Res. 2000, 75, 167-175. 12. Degl’Innocenti, A.; Pollicino, S.; Capperucci, A. Chem. Commun. 2006, 4881-4893, and references cited therein. 13. Capperucci, A.; Tanini, D.; Borgogni, C.; Degl’Innocenti, A. Heteroatom Chem. 2014, 678-683. 14. Tanini, D.; Degl’Innocenti, A.; Capperucci, A. Eur. J. Org. Chem. 2015, 357-369. 15. Capperucci, A.; Tanini, D. Phosphorus Sulfur Silicon Relat. Elem. 2015, 190, 1320-1338. 16. Degl’Innocenti, A.; Capperucci, A.; Cerreti, A.; Pollicino, S.; Scapecchi, S.; Malesci, I.; Castagnoli, G. Synlett 2005, 3063-3066. 17. Salvatore, R. N.; Smith, R. A.; Nischwitza, A. K.; Gavin, T. Tetrahedron Lett. 2005, 46, 8931-8935. 18. Treatment of methyl 2-(3-(allyloxy)-2-hydroxypropylthio)acetate (R = CH2 OAll) (0.4 mmol) with DIBAL-H (0.48 mmol) in dry toluene21 for 3 h, at −78°C, led to 6-(allyloxymethyl)-1,4-oxathian-2-ol 3a (63%). Diastereomeric ratio = 65:35. 1 H NMR (400 MHz, CDCl3 ), δ (ppm): 2.27–2.40 (1 H, m), 2.45–2.6 (2 H, m), 2.72 (1 H, dd, J = 11.2, 13.4 Hz), 2.88–2.96 (1 H, m), 3.0 (1 H, dd, J = 3.1, 12.5 Hz), 3.09 (1 H, dd, J = 2.1, 13.4 Hz), 3.23 (1 H, ap d, ls = 15.0 Hz), 3.37 (1 H, dd, J = 5.4, 10.0 Hz), 3.43 (1 H, dd, J = 4.2, 5.8 Hz), 3.46 (1 H, dd, J = 3.7, 5.8 Hz), 3.61 (1 H, dd, J = 5.4, 10.3 Hz), 3.71 (1 H, dd, J = 4.9, 10.3 Hz), 4.0–4.07 (4 H, m), 4.29–4.35 (1 H, m), 4.59–4.66 (1 H, m), 4.97 (1 H, dd, J = 3.5, 7.6 Hz), 5.18–5.32 (5 H, m), 5.84–5.96 (2 H, m). 13 C NMR (100 MHz, CDCl3 ), δ (ppm): = 27.4, 28.5, 31.4, 32.5, 67.4, 70.7, 72.3, 72.5, 72.6, 78.0, 87.9, 95.8, 117.4, 117.6, 134.3, 134.4. MS m/z (%): 190 (2) [M+. ], 188 (8), 147 (3), 119 (10), 89 (28), 73 (20), 61 (30), 41 (100).
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19. Tanini, D.; Barchielli, G.; Benelli, F.; Degl’Innocenti, A.; Capperucci, A. Phosphorus Sulfur Silicon Relat. Elem. 2015, 190, 1265-1270. 20. Characteristic data: Diastereomeric ratio = 60:40. 1 H NMR (400 MHz, CDCl3 ), δ (ppm): 2.43–2.56 (4 H, m), 2.70–2.72 (4 H, m), 3.42– 3.67 (4 H, m), 4.11–4.16 (1 H, m, CHCH2 Cl), 4.41–4.44 (1 H, m,
CHCH2 Cl), 5.08 (1 H, bd, J = 9.3 Hz, CHOH), 5.21 (1 H, bd, J = 7.7 Hz, CHOH). 13 C NMR (100 MHz, CDCl3 ), δ (ppm): = 18.5, 21.5, 29.6, 30.3, 47.2, 47.3, 78.4, 80.6, 96.9, 99.8. 21. Tiecco, M.; Testaferri, L.; Marini, F.; Sternativo, S.; Santi, C.; Bagnoli, L.; Temperini, A. Tetrahedron. 2007, 63, 5482-5489.
